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Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure
- Source :
- Circulation
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- Supplemental Digital Content is available in the text.<br />Background: SGLT2 (sodium-glucose cotransporter-2) inhibitors improve heart failure–associated outcomes in patients with type 2 diabetes. In patients with heart failure, SGLT2 inhibitors will likely be coprescribed with a loop diuretic, but this combined effect is not well-defined. Our aim was to assess the diuretic and natriuretic effect of empagliflozin in combination with loop diuretics. Methods: The RECEDE-CHF trial (SGLT2 Inhibition in Combination With Diuretics in Heart Failure) was a randomized, double-blind, placebo-controlled, crossover trial of patients with type 2 diabetes and heart failure with reduced ejection fraction taking regular loop diuretic who were randomized to empagliflozin 25 mg once daily or placebo for 6 weeks with a 2-week washout period. The primary outcome was change in 24-hour urinary volume from baseline to week 6. Results: Twenty-three participants (mean age, 69.8 years; 73.9% male; mean furosemide dose, 49.6±31.3 mg/d; mean HbA1c, 7.9±3.8%) were recruited. Compared with placebo, empagliflozin caused a significant increase in 24-hour urinary volume at both day 3 (mean difference, 535 mL [95% CI, 133–936]; P=0.005) and week 6 (mean difference, 545 mL [95% CI, 136–954]; P=0.005) after adjustment for treatment order, baseline 24-hour urine volume, and percentage change in loop diuretic dose. At 6 weeks, empagliflozin did not cause a significant change in 24-hour urinary sodium (mean difference, −7.85 mmol/L [95% CI, −2.43 to 6.73]; P=0.57). Empagliflozin caused a nonsignificant increase in fractional excretion of sodium at day 3, which was absent at week 6 (mean difference day 3, 0.30% [95% CI, −0.03 to 0.63]; P=0.09; week 6, 0.11% [95% CI, −0.22 to 0.44]; P>0.99), and a significant increase in electrolyte-free water clearance at week 6 (mean difference, 312 mL [95% CI, 26–598]; P=0.026) compared with placebo. Empagliflozin also caused significant reductions in body weight and serum urate at week 6. Conclusions: Empagliflozin caused a significant increase in 24-hour urine volume without an increase in urinary sodium when used in combination with loop diuretic. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03226457.
- Subjects :
- Male
medicine.medical_specialty
Type 2 diabetes
030204 cardiovascular system & hematology
Diabetes Complications
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Glucosides
Sodium Potassium Chloride Symporter Inhibitors
Original Research Articles
Physiology (medical)
Diabetes mellitus
Internal medicine
Humans
Medicine
In patient
furosemide
030212 general & internal medicine
Benzhydryl Compounds
Sodium-Glucose Transporter 2 Inhibitors
Aged
Heart Failure
business.industry
Furosemide
medicine.disease
diuretics
Diabetes Mellitus, Type 2
Heart failure
diabetes mellitus
Chronic Disease
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 142
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....4810d6ea1dc4b88601ffdbd78b79bc21